Glibenclamide, a specific inhibitor of ATP-sensitive K⁺ channels, inhibits coronary vasodilation induced by angiotensin II-receptor antagonists

The purpose of our study was test the hypothesis that endogenous angiotensin II contributes to the basal coronary artery tone by acting at vascular ATP-sensitive K⁺ (K⁺ATP) channels. Coronary blood flow (CBF) and other hemodynamic parameters were measured in anesthetized dogs. Intracoronary infusion of the selective antagonists of angiotensin II AT₁ receptors (L-158,809 and E4177) increased CBF without affecting other hemodynamic parameters, indicating that endogenous angiotensin II caused coronary vasoconstriction through the AT₁ subtype receptors. Coronary vasodilation in response to AT₁ receptor antagonists was blunted by pretreatment with glibenclamide (a specific inhibitor of K⁺ATP channels; p < 0.01) but not by either an adenosine-receptor antagonist or an inhibitor of nitric oxide synthesis. Coronary vasodilation in response to AT₁-receptor antagonists was partly reduced (p < 0.01) by PD-123319 (the AT₂-receptor antagonist). Glibenclamide had no effect on coronary vasodilation induced by sodium nitroprusside. These results indicate that in dogs in vivo, coronary vasodilation in response to AT₁-receptor antagonists inhibited markedly by glibenclamide and partly by PD-123319, suggesting that endogenous angiotensin II contributes to the maintenance of basal coronary vascular tone by acting at K⁺ATP channels through its receptors.